Human nuclear clusterin mediates apoptosis by interacting with Bcl-XL through C-terminal coiled coil domain.
Clusterin (CLU), a glycoprotein, is involved in apoptosis, producing two alternatively spliced isoforms in various cell types. The pro-apoptotic CLU appears to be a nuclear isoform (nuclear clusterin; nCLU), and the secretory CLU (sCLU) is thought to be anti-apoptotic. The detailed molecular mechanism of nCLU as a pro-apoptotic molecule has ... not yet been clear. In the current study, overexpressed nCLU induced apoptosis in human kidney cells. Biochemical studies revealed that nCLU sequestered Bcl-XL via a putative BH3 motif in the C-terminal coiled coil (CC2) domain, releasing Bax, and promoted apoptosis accompanied by activation of caspase-3 and cytochrome c release. These results suggest a novel mechanism of apoptosis mediated by nCLU as a pro-apoptotic molecule.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Apoptosis, Cell Line, Tumor, Cell Survival, Clusterin, HEK293 Cells, Humans, Keratinocytes, Male, Molecular Sequence Data, Prostatic Neoplasms, Protein Interaction Domains and Motifs, Protein Structure, Tertiary, bcl-X Protein
Amino Acid Motifs, Amino Acid Sequence, Apoptosis, Cell Line, Tumor, Cell Survival, Clusterin, HEK293 Cells, Humans, Keratinocytes, Male, Molecular Sequence Data, Prostatic Neoplasms, Protein Interaction Domains and Motifs, Protein Structure, Tertiary, bcl-X Protein
J. Cell. Physiol.
Date: Mar. 01, 2012
PubMed ID: 21567405
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